Meiotic and sperm aneuploidy studies in three carriers of Robertsonian translocations and small supernumerary marker chromosomes

Abstract

Objective: To study the meiotic behaviour of one carrier of a small supernumerary marker chromosome (sSMC): 47,XY,+mar; one carrier of a Robertsonian translocation (ROB): 45,XY,rob(13;21) (q10;q10); and one carrier of both a sSMC and a ROB: 46,XY,rob(13;21) (q11.1;q11.1),+mar.

Design: Case-control study.

Setting: University-affiliated research center and hospital.

Patient(s): Subfertile men with ROB and sSMC.

Intervention(s): None.

Main outcome measure(s): The chromosomal origin of the sSMC was assessed by multiplex fluorescence in situ hybridization. The segregation of the ROB and sSMC in sperm and possible interchromosomal effects were examined by fluorescence in situ hybridization. Synapsis, meiotic recombination, and meiotic inactivation were investigated in ejaculate spermatocytes of the 47,XY,+mar and 45,XY,rob(13;21) carriers using immunostaining.

Result(s): In the 47,XY,+mar and 46,XY,rob(13;21),+mar carriers, the sSMC was found in 13.5% and 11.5 % of sperm, respectively. Analysis of meiotic segregation of chromosome 13 and 21 showed that 91.2% of sperm were normal/balanced in the 46,XY,rob(13;21),+mar case, whereas 88.4% of sperm were normal/balanced in the 45,XY,rob(13;21) case. Interchromosomal effects involving the sex chromosomes were found in both sSMC carriers. Both 47,XY,+mar and 45,XY,rob(13;21) carriers showed decreased global recombination, impaired synapsis, and an association of abnormal chromosomes with the XY body.

Conclusion(s): Carriers of marker chromosomes produce sperm with markers at frequencies lower than theoretically expected. Carriers of ROB and sSMC showed decreased recombination, impaired synapsis, and association of abnormal chromosomes with the XY body, which may contribute to an interchromosomal effect. Using immunofluorescence techniques to analyze ejaculate-derived spermatocytes from subfertile men provides a novel technique for examining meiosis without the need for a testicular biopsy.

Keywords: Meiotic recombination; Robertsonian translocation; interchromosomal effects; sex body association; small supernumerary marker chromosomes.